SCIENTISTS STUDY HOW LIGHT ACTIVATES
ST. JOHN'S WORT CHEMICAL

Known to be super-toxic to viruses,
cancer cells

UPTON, NY -- A team of scientists has made progress in determining how hypericin,
a chemical found naturally in the herbal remedy plant St. John's wort, becomes
super-toxic to viruses and cancer cells when exposed to light.

The results were published today in the Journal
of the American Chemical Society by chemists from Iowa
State University and the U.S. Department of Energy's
Brookhaven National Laboratory.

The research shows that when light strikes the
hypericin molecule, it triggers a chemical reaction called a double proton
transfer. This discovery raises the possibility that hypericin and similar
molecules that are also activated by light could be used in therapies to
treat AIDS, hepatitis, brain tumors, and other diseases.

Hypericin's disease-fighting properties are not
yet clinically proven, but are now being evaluated in clinical trials.

"The Iowa State team has long been investigating
how hypericin and related chemicals kill viruses when exposed to light,"
said BNL chemist Edward Castner. "Through our collaboration with them,
we have now verified their hypothesis about the mechanism for that effect.
Knowing this may be an important step toward harnessing hypericin's power
for more effective disease treatment."

From Cow Pasture to Chemistry Lab

The study traces its roots back to the mystery
of cows that became sick after grazing on the yellow-flowered plant on sunny
days, but recovered when moved to a dark barn. The animals were suffering
from hypericism, or extreme sensitivity to light, caused by the hypericin
in the St. John's wort.

In 1991, Iowa State scientists demonstrated that
hypericin must be exposed to light in order to kill viruses. Their experiments
showed that hypericin was effective in killing many kinds of lentiviruses,
especially the equine infectious anemia virus (EIAV), a retrovirus genetically
related to the human AIDS virus, HIV. This and other studies led to early
tests of
hypericin as an anti-AIDS drug.

Even as more clinical trials began, Iowa State chemists tried to find out
how hypericin works. Early results showed that light exposure caused hypericin
to transfer energy to nearby oxygen molecules, producing a damaging product
called singlet oxygen that is highly toxic to viruses and bacteria. But
later experiments showed that hypericin was still toxic even when no nearby
oxygen was available.

Continued work suggested that another light-driven
chemical process, called a proton transfer reaction, might be responsible
for the toxic effect. In hypericin, proton transfer reactions occur when
a proton, or positively charged hydrogen atom, moves a short distance of
less than 2 Angstroms (8 billionths of an inch) between neighboring oxygen
atoms on the molecule.
Using very short bursts of light from a laser, the Iowa group led by Jacob
Petrich developed a theory that light causes hypericin to undergo two of
the proton transfer reactions at the same time, one on either side of the
molecule.

To arrive at that hypothesis, Petrich and his team
had to capture the fleeting light emission given off by hypericin after
it absorbed a light pulse lasting less than 100 femtoseconds, or quadrillionths
of a second. They were able to observe the signal caused by the proton-transfer
reaction as it occurred lasting only 7 picoseconds, or trillionths
of a second.

"Sometimes the proton isn't transferred directly,
but falls off and is absorbed in the water surrounding the hypericin,"
said Castner. "This proton ejection, which causes the surrounding area
to become more acidic, may be important to hypericin's toxicity to viruses.
We already know that certain parts of the HIV virus can be damaged by too
much acidity."

A control experiment showed that the process didn't
occur in a chemically modified form of hypericin in which all the protons
that would have transferred had been replaced by methyl groups.

The BNL experiment that confirmed the theory is
called fluorescence upconversion spectroscopy. It uses a laser in Brookhaven's
Chemistry Department to produce the light pulses and "turn on"
the chemical reaction. The apparatus allows the scientists to "watch"
the molecules move by carefully recording the intensity and color of the
light emitted from the hypericin over time after the light burst. The apparatus
is now being duplicated at Iowa State.

Meanwhile, the Delaware-based biotechnology firm
VIMRX is testing a synthetic form of hypericin in clinical trials for use
against the AIDS virus HIV, hepatitis C, and glioblastoma, a highly malignant
form of brain tumor. In October, the University of Pennsylvania began a
VIMRX-sponsored trial of topically-applied hypericin for skin diseases including
psoriasis, cutaneous T-cell lymphoma and warts.

Besides Castner and Petrich, the collaboration
included Iowa State Ph.D. candidate Doug English, postdoctoral fellow Kaustav
Das, and scientists Kyle Ashby and Jaehun Park. The research at Iowa State
was supported by the National Science Foundation. Brookhaven's research
was funded by DOE.

Brookhaven National Laboratory carries out basic
and applied research in the physical, biomedical and environmental sciences
and in selected energy technologies. BNL is operated by Associated Universities,
Inc., a nonprofit research management organization, under contract with
the U.S. Department of Energy.